Table_2_PET/CT-Based Characterization of 18F-FDG Uptake in Various Tissues Reveals Novel Potential Contributions to Coronary Artery Disease in Psoriatic Arthritis.docx

Background and ObjectivesPsoriasis is a heterogeneous inflammatory disease that involves the skin, joints, liver, heart, and other organs. Psoriatic arthritis (PsA) is associated with cardiovascular disease (CVD), but the relative contributions of inflammatory and metabolic dysregulation to CVD are incompletely understood. We set out to discover novel potential contributors to CVD in PsA patients by comprehensively phenotyping a cohort of PsA patients using these advanced technologies.
MethodsIn this cross-sectional analysis of a cohort study, we investigated associations of systemic inflammation and metabolic dysregulation with Coronary CT angiography (CCTA)-proven coronary artery disease (CAD) in 39 subjects with PsA. We measured traditional CVD risk factors [blood pressure, Body Mass Index (BMI), diabetes, age, sex, smoking], serum markers of systemic inflammation (hsCRP, GlycA) and metabolic dysfunction (cholesterol efflux capacity), and inflammatory cytokines (IL-1β, IL-6, IL-12/IL-23, IL-17A, TNF-α, IFN-γ). We also incorporated radiographic measures of metabolic dysfunction (visceral and subcutaneous adipose volume) and tissue-specific inflammation (positron emission tomography-computed tomography, PET-CT). To quantify relative contributions of FDG (fluorodeoxyglucose) uptake and adiposity to coronary plaque, we performed multiple linear regression, controlling for Framingham risk score (FRS) and FRS + visceral adiposity.
ResultsCompared with non-psoriatic volunteers, subjects with PsA had elevated markers of metabolic and inflammatory disease, which was more pronounced in subjects with moderate-to-severe skin disease. This included visceral (p = 0.005) and subcutaneous (p = 0.004) adiposity, BMI (p = 0.001), hemoglobin A1C (p = 0.037), high sensitivity C-reactive protein (p = 0.005), IL-6 (p = 0.003), IFN-γ (p = 0.006), and liver FDG uptake (p = 0.03). In subjects with PsA, visceral adiposity correlated significantly with subclinical CAD (standardized β = 0.681, p = 0.002), as did FDG uptake in bone marrow (standardized β = 0.488, p = 0.008), liver (standardized β = 0.619, p < 0.001), spleen (standardized β = 0.523, p = 0.004), and subcutaneous adipose (standardized β = 0.524, p = 0.003).
InterpretationTogether, these findings reveal inflammatory and metabolic potential contributors to subclinical CAD in PsA, including adipose inflammation, and suggesting novel targets for CVD prevention and treatment in PsA.

背景与研究目的
银屑病（Psoriasis）是一种累及皮肤、关节、肝脏、心脏等多个器官的异质性炎症性疾病。银屑病关节炎（Psoriatic arthritis, PsA）与心血管疾病（cardiovascular disease, CVD）相关，但炎症与代谢失调对心血管疾病的相对贡献尚未完全阐明。本研究旨在通过先进技术对银屑病关节炎患者队列进行全面表型分析，以挖掘银屑病关节炎患者并发心血管疾病的新型潜在致病因素。

研究方法
本项队列研究的横断面分析中，纳入39名银屑病关节炎患者，探究全身炎症、代谢失调与经冠状动脉CT血管造影（Coronary CT angiography, CCTA）证实的冠状动脉粥样硬化性心脏病（Coronary artery disease, CAD）之间的关联。我们检测了传统心血管疾病危险因素[血压、体质量指数（Body Mass Index, BMI）、糖尿病、年龄、性别、吸烟史]、全身炎症血清标志物[高敏C反应蛋白（hsCRP）、GlycA]、代谢功能异常标志物（胆固醇流出能力）以及炎症细胞因子[IL-1β、IL-6、IL-12/IL-23、IL-17A、TNF-α、IFN-γ]。同时纳入代谢功能异常的影像学指标[内脏脂肪与皮下脂肪体积]以及组织特异性炎症的检测结果[正电子发射计算机断层显像（positron emission tomography-computed tomography, PET-CT）]。为量化氟脱氧葡萄糖（fluorodeoxyglucose, FDG）摄取量与体脂对冠状动脉斑块的相对贡献，我们采用多重线性回归分析，并校正弗雷明汉风险评分（Framingham risk score, FRS）以及FRS联合内脏脂肪量作为混杂因素。

研究结果
与非银屑病志愿者相比，银屑病关节炎患者的代谢与炎症相关标志物水平升高，且在中重度皮肤受累患者中该现象更为显著。具体包括内脏脂肪（p=0.005）、皮下脂肪（p=0.004）、体质量指数（p=0.001）、糖化血红蛋白（hemoglobin A1C）（p=0.037）、高敏C反应蛋白（p=0.005）、IL-6（p=0.003）、IFN-γ（p=0.006）以及肝脏FDG摄取量（p=0.03）。在银屑病关节炎患者中，内脏脂肪量与亚临床冠状动脉粥样硬化性心脏病显著相关（标准化β=0.681，p=0.002），骨髓（标准化β=0.488，p=0.008）、肝脏（标准化β=0.619，p<0.001）、脾脏（标准化β=0.523，p=0.004）以及皮下脂肪（标准化β=0.524，p=0.003）的FDG摄取量同样与亚临床CAD显著相关。

研究解读
综合上述结果，本研究明确了银屑病关节炎患者并发亚临床冠状动脉粥样硬化性心脏病的炎症与代谢相关潜在致病因素，其中包括脂肪组织炎症，同时为银屑病关节炎患者的心血管疾病防治提供了新型潜在靶点。